New Oldowan locality Sare-Abururu (ca. 1.7 Ma) provides evidence of diverse hominin behaviors on the Homa Peninsula, Kenya.

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3-2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition.

Glacial vicariance and secondary contact shape demographic histories in a freshwater mussel species complex.

Characterizing the mechanisms influencing the distribution of genetic variation in aquatic species can be difficult due to the dynamic nature of hydrological landscapes. In North America's Central Highlands, a complex history of glacial dynamics, long-term isolation, and secondary contact have shaped genetic variation in aquatic species. Although the effects of glacial history have been demonstrated in many taxa, responses are often lineage- or species-specific and driven by organismal ecology. In this study, we reconstruct the evolutionary history of a freshwater mussel species complex using a suite of mitochondrial and nuclear loci to resolve taxonomic and demographic uncertainties. Our findings do not support Pleurobema rubrum as a valid species, which is proposed for listing as threatened under the U.S. Endangered Species Act. We synonymize P. rubrum under Pleurobema sintoxia-a common and widespread species found throughout the Mississippi River Basin. Further investigation of patterns of genetic variation in P. sintoxia identified a complex demographic history, including ancestral vicariance and secondary contact, within the Eastern Highlands. We hypothesize these patterns were shaped by ancestral vicariance driven by the formation of Lake Green and subsequent secondary contact after the last glacial maximum. Our inference aligns with demographic histories observed in other aquatic taxa in the region and mirrors patterns of genetic variation of a freshwater fish species (Erimystax dissimilis) confirmed to serve as a parasitic larval host for P. sintoxia. Our findings directly link species ecology to observed patterns of genetic variation and may have significant implications for future conservation and recovery actions of freshwater mussels.

Breathing is coupled with voluntary initiation of mental imagery.

Previous research has suggested that bodily signals from internal organs are associated with diverse cortical and subcortical processes involved in sensory-motor functions, beyond homeostatic reflexes. For instance, a recent study demonstrated that the preparation and execution of voluntary actions, as well as its underlying neural activity, are coupled with the breathing cycle. In the current study, we investigated whether such breathing-action coupling is limited to voluntary motor action or whether it is also present for mental actions not involving any overt bodily movement. To answer this question, we recorded electroencephalography (EEG), electromyography (EMG), and respiratory signals while participants were conducting a voluntary action paradigm including self-initiated motor execution (ME), motor imagery (MI), and visual imagery (VI) tasks. We observed that the voluntary initiation of ME, MI, and VI are similarly coupled with the respiration phase. In addition, EEG analysis revealed the existence of readiness potential (RP) waveforms in all three tasks (i.e., ME, MI, VI), as well as a coupling between the RP amplitude and the respiratory phase. Our findings show that the voluntary initiation of both imagined and overt action is coupled with respiration, and further suggest that the breathing system is involved in preparatory processes of voluntary action by contributing to the temporal decision of when to initiate the action plan, regardless of whether this culminates in overt movements.

Depressive rumination is correlated with brain responses during self-related processing.

BACKGROUND: Rumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging because of the need to distinguish self effects from the emotional content of task stimuli. This study employed an emotionally neutral self-related paradigm to investigate possible altered self-processing in depression and its link to rumination. METHODS: People with major depressive disorder (n = 25) and controls (n = 25) underwent task-based electro-encephalogram recording. We studied late event-related potentials, along with low-frequency oscillatory power. We compared electroencephalogram metrics between groups and correlated them with depressive symptoms and reported rumination. RESULTS: Participants with major depressive disorder displayed a difference in late positive potentials across frontocentral electrodes between self-related and non-self-related conditions. We found no such difference in controls. The magnitude of this difference was positively correlated with depressive symptoms and reported rumination. Participants with major depressive disorder also had elevated theta oscillation power at central electrodes in self-related conditions, a finding that we did not see in controls. LIMITATIONS: Patients with major depressive disorder were medicated at the time of the study. The group studied was primarily female, so the observed effects may have been sex-specific. CONCLUSION: Rumination appears to be linked to altered self-related processing in depression, independent of stimuli-related emotional confounds. This connection between self-related processing and depression may point to a self disorder as a core component of depression.

Increases in HIV status disclosure and sexual communication between South African men who have sex with men and their partners following use of HIV self-testing kits.

Availability of HIV self-testing may increase HIV testing frequency among men who have sex with men (MSM). It is unclear, however, if self-testing may impact HIV-related sexual behaviors among MSM, including HIV status disclosure and condom use. We conducted a mixed methods analysis of changes in HIV-related behaviors after HIV self-testing introduction, using data from 110 MSM participating in a feasibility and acceptability study of HIV self-testing in Mpumalanga Province, South Africa. We found increased HIV status disclosure from study participants to sexual partners after HIV self-testing introduction, from 61.8% at baseline to 75.5% at 6-month follow-up (p = 0.04), but decreased condom use with female partners (p = 0.03). Qualitative interviews reveal that some participants used test results to inform condom use. Distribution of self-testing kits can improve mutual disclosure, but should be accompanied by information stressing that the tests may not detect early HIV infections or other sexually transmitted infections.

Intrinsic activity temporal structure reactivity to behavioural state change is correlated with depressive symptoms.

The brain's intrinsic activity plays a fundamental role in its function. In normal conditions this activity is responsive to behavioural context, changing as an individual switches between directed tasks and task-free conditions. A key feature of such changes is the movement of the brain between corresponding critical and sub-critical states, with these dynamics supporting efficient cognitive processing. Breakdowns in processing efficiency can occur, however, in brain disorders such as depression. It was therefore hypothesised that depressive symptoms would be related to reduced intrinsic activity responsiveness to changes in behavioural state. This was tested in a mixed group of major depressive disorder patients (n = 26) and healthy participants (n = 37) by measuring intrinsic EEG activity temporal structure, quantified with detrended fluctuation analysis (DFA), in eyes-closed (EC) and eyes-open task-free states and contrasting between the conditions. The degree to which DFA values changed between the states was found to correlate negatively with depressive symptoms. DFA values did not differ between states in those with higher symptom levels, meaning that the brain remained in a less flexible sub-critical condition. This sub-critical condition in the EC state was further found to correlate with levels of maladaptive rumination. This may reflect a general cognitive inflexibility resulting from a lack in neural activity reactivity that may predispose people to overly engage in self-directed attention. These results provide an initial link between intrinsic activity reactivity and psychological features found in psychiatric disorders.

The Application of Commercially Available Mobile Cigarette Topography Devices for E-cigarette Vaping Behavior Measurements.

INTRODUCTION: The ability to reliably measure real-world vaping behavior is critical to understand exposures to potential toxins. Commercially available mobile topography devices were originally designed to measure cigarette puffing behavior. Information regarding how applicable these devices are to the measurement of electronic cigarette (e-cigarette) vaping topography is needed. METHODS: Clinical Research Support System (CReSS; Pocket) and Smoking Puff Analyzer Mobile (SPA-M) topography devices were tested against the calibrated laboratory-based smoking puff analyzer duplicator (SPA-D) device combined with an analytical smoking machine that generates programmable puffs with high precision. Puff topography of e-cigarettes was measured over a range of puff volumes (10-130 mL) at 2 and 5 s puff durations (using bell- and square-shaped puffs). "Real-world" topography data collected from 10 participants during 1 week of at-home vaping were also analyzed. Recording anomalies and limitations of the devices, such as accuracy of detection of the puff end, flow rate dropouts, unreported puffs, and abandoned vaping sessions for the CReSS, and multi-peak puffs for the SPA-M were defined. RESULTS: The accuracy of puff volumes and durations was determined for both devices. The error for SPA-M was generally within ±10%, whereas that for the CReSS varied more widely. The CReSS consistently underestimated puff duration at higher flow rates. CONCLUSIONS: CReSS and SPA-M topography devices can be used for real-world e-cigarette topography measurements, but researchers have to be aware of the limitations. Both devices can provide accurate measurements only under certain puff parameter ranges. The SPA-M provided more accurate measurements under a wider range of puffing parameters than the CReSS. Summary data reported by both devices require thorough analysis of the raw data to avoid misleading data interpretation. IMPLICATIONS: Results of this study provide researchers with valuable information about the capability of commercially available cigarette topography devices to measure real-world vaping behaviors. The differing measurement ranges of the two devices and puff recording limitations and anomalies should be taken into account during analysis and interpretation of real-world data.

The minimal self hypothesis.

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of "self" and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate "self," and employed it to explain some psychopathological symptoms. In those studies, "self" is understood in a minimalist sense, sheer "for-me-ness." Unfortunately, explication of the "minimal self" (MS) has relied on conceptual analysis, and applications to psychopathology have been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS's current scientific status is analogous to that of the "atom," at the time when "atom" was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for "MS." Discovery of the brain's Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit "MS" can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that "levels of consciousness" (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation-a bifurcation point-for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness.

Instability of brain connectivity during nonrapid eye movement sleep reflects altered properties of information integration.

Nonrapid eye movement (NREM) sleep is associated with fading consciousness in humans. Recent neuroimaging studies have demonstrated the spatiotemporal alterations of the brain functional connectivity (FC) in NREM sleep, suggesting the changes of information integration in the sleeping brain. However, the common stationarity assumption in FC does not satisfactorily explain the dynamic process of information integration during sleep. The dynamic FC (dFC) across brain networks is speculated to better reflect the time-varying information propagation during sleep. Accordingly, we conducted simultaneous EEG-fMRI recordings involving 12 healthy men during sleep and observed dFC across sleep stages using the sliding-window approach. We divided dFC into two aspects: mean dFC (dFCmean ) and variance dFC (dFCvar ). A high dFCmean indicates stable brain network integrity, whereas a high dFCvar indicates instability of information transfer within and between functional networks. For the network-based dFC, the dFCvar were negatively correlated with the dFCmean across the waking and three NREM sleep stages. As sleep deepened, the dFCmean decreased (N0~N1 > N2 > N3), whereas the dFCvar peaked during the N2 stage (N0~N1 < N3 < N2). The highest dFCvar during the N2 stage indicated the unstable synchronizations across the entire brain. In the N3 stage, the overall disrupted network integration was observed through the lowest dFCmean and elevated dFCvar, compared with N0 and N1. Conclusively, when the network specificity (dFCmean ) breaks down, the consciousness dissipates with increasing variability of information exchange (dFCvar ).

Regioselective Iron-Catalyzed [2 + 2 + 2] Cycloaddition Reaction Forming 4,6-Disubstituted 2-Aminopyridines from Terminal Alkynes and Cyanamides.

Iron complexes bound by redox-active pyridine dialdimine (PDAI) ligands catalyze the cycloaddition of two terminal alkynes and one cyanamide. The reaction is both chemo- and regioselective, as only 4,6-disubstituted 2-aminopyridine products are formed in moderate to high yields. Isolation of an iron azametallacycle (4) suggests that catalyst deactivation occurs with a large excess of cyanamide over longer reaction times. Fe-catalyzed cycloaddition allowed for a straightforward synthesis of a variety of aminopyridines, including known estrogen receptor ligands.

HIV risk and prevention among men who have sex with men in rural South Africa.

Rural South African men who have sex with men (MSM) are likely to be underserved in terms of access to relevant healthcare and HIV prevention services. While research in urban and peri-urban MSM populations has identified a range of factors affecting HIV risk in South African MSM, very little research is available that examines HIV risk and prevention in rural MSM populations. This exploratory study begins to address this lack by assessing perceptions of HIV risk among MSM in rural Limpopo province. Using thematic analysis of interview and discussion data, two overarching global themes that encapsulated participants' understandings of HIV risk and the HIV risk environment in their communities were developed. In the first theme, "community experience and the rural social environment", factors affecting HIV risk within the broad risk environment were discussed. These included perceptions of traditional value systems and communities as homophobic; jealousy and competition between MSM; and the role of social media as a means of meeting other MSM. The second global theme, "HIV/AIDS knowledge, risk and experience", focused on factors more immediately affecting HIV transmission risk. These included: high levels of knowledge of heterosexual HIV risk, but limited knowledge of MSM-specific risk; inconsistent condom and lubricant use; difficulties in negotiating condom and lubricant use due to uneven power dynamics in relationships; competition for sexual partners; multiple concurrent sexual partnerships; and transactional sex. These exploratory results suggest that rural South African MSM, like their urban and peri-urban counterparts, are at high risk of contracting HIV, and that there is a need for more in-depth research into the interactions between the rural context and the specific HIV risk knowledge and behaviours that affect HIV risk in this population.

Design and Validation of a Research-Grade Waterpipe Equipped With Puff Topography Analyzer.

INTRODUCTION: Worldwide, commercially available waterpipes vary widely in design and durability, including differences in fabrication materials, degree of leak-tight fit, and flow path diameter. Little is known about how the components of the waterpipe may influence puffing behavior and user's exposure to toxins. To systematically evaluate exposure, it is necessary to use a standardized research-grade waterpipe (RWP) when conducting clinical and laboratory-based trials. METHODS: We developed a RWP that is configured with an in-line topography system which allows real-time measurement and recording of the smoke volume drawn through the RWP. The RWP was calibrated across the flow rate range expected for waterpipe tobacco smoking and the calibration was verified for known puff volumes using a smoking machine. Operation of the RWP was qualified in a cohort of experienced waterpipe smokers, each smoker using the RWP ad libitum in a laboratory setting while smoker topography and subjective effects data were collected. RESULTS: RWP machine smoking was highly reproducible and yielded puff volumes that agreed well with true values. User acceptance was comparable, and puffing behavior was similar in pattern, with more frequent puffing in the beginning of the session, but significantly different in intensity from that used to estimate the majority of toxicant exposure reported in the literature. CONCLUSIONS: The RWP operates with known precision and accuracy and is well accepted by experienced smokers. This tool can be used to determine the extent to which puffing behaviors are affected by the waterpipe design, components, and/or accessories, tobacco nicotine content, sweet flavorings and/or additives known to increase addictiveness. IMPLICATIONS: This study describes a standardized RWP, equipped with a puffing topography analyzer, which can operate with known precision and accuracy, and is well-accepted by experienced smokers in terms of satisfaction and reward. The RWP is an important tool for determining if puffing behaviors, and thus estimated toxin exposures, are affected by the waterpipe design, components, and/or accessories, tobacco nicotine content, sweet flavorings, and/or additives that are known to increase addictiveness.

Attention and memory-driven effects in action studies.

We provide empirical examples to conceptually clarify some items on Firestone & Scholl's (F&S's) checklist, and to explain perceptual effects from an attentional and memory perspective. We also note that action and embodied cognition studies seem to be most susceptible to misattributing attentional and memory effects as perceptual, and identify four characteristics unique to action studies and possibly responsible for misattributions.

GABAA receptor deficits predict recovery in patients with disorders of consciousness: A preliminary multimodal [(11) C]Flumazenil PET and fMRI study.

OBJECTIVES: Disorders of consciousness (DoC)-that is, unresponsive wakefulness syndrome/vegetative state and minimally conscious state-are debilitating conditions for which no reliable markers of consciousness recovery have yet been identified. Evidence points to the GABAergic system being altered in DoC, making it a potential target as such a marker. EXPERIMENTAL DESIGN: In our preliminary study, we used [(11) C]Flumazenil positron emission tomography to establish global GABAA receptor binding potential values and the local-to-global (LTG) ratio of these for specific regions. These values were then compared between DoC patients and healthy controls. In addition, they were correlated with behavioral improvements for the patients between the time of scanning and 3 months later. Functional magnetic resonance imaging resting-state functional connectivity was also calculated and the same comparisons made. PRINCIPAL OBSERVATIONS: lobal GABAA receptor binding was reduced in DoC, as was the LTG ratio in specifically the supragenual anterior cingulate. Both of these measures correlated with behavioral improvement after 3 months. In contrast to these measures of GABAA receptor binding, functional connectivity did not correlate with behavioral improvement. CONCLUSIONS: Our preliminary findings point toward GABAA receptor binding being a marker of consciousness recovery in DoC.

Ovariectomy expands murine short-term hemopoietic stem cell function through T cell expressed CD40L and Wnt10B.

Estrogen deficiency expands hemopoietic stem and progenitor cells (HSPCs) and mature blood lineages, but the involved mechanism and the affected HSPC populations are mostly unknown. Here we show that ovariectomy (ovx) expands short-term HSPCs (ST-HSPCs) and improves blood cell engraftment and host survival after bone marrow (BM) transplantation through a dual role of the T-cell costimulatory molecule CD40 ligand (CD40L). This surface receptor is required for ovx to stimulate T-cell production of Wnt10b, a Wnt ligand that activates Wnt signaling in HSPCs and stromal cells (SCs). Moreover, CD40L is required for ovx to increase SC production of the hemopoietic cytokines interleukin (IL)-6, IL-7, and granulocyte macrophage-colony-stimulating factor. Attesting to the relevance of CD40L and Wnt10b, ovx fails to expand ST-HSPCs in CD40L-null mice and in animals lacking global or T-cell expression of Wnt10b. In summary, T cells expressed CD40L, and the resulting increased production of Wnt10b and hemopoietic cytokines by T cells and SCs, respectively, plays a pivotal role in the mechanism by which ovx regulates hemopoiesis. The data suggest that antiestrogens may represent pharmacological targets to improve ST-HSPC function through activation of the microenvironment.

Notch1 regulates angio-supportive bone marrow-derived cells in mice: relevance to chemoresistance.

Host responses to chemotherapy can induce resistance mechanisms that facilitate tumor regrowth. To determine the contribution of bone marrow-derived cells (BMDCs), we exposed tumor-bearing mice to chemotherapeutic agents and evaluated the influx and contribution of a genetically traceable subpopulation of BMDCs (vascular endothelial-cadherin-Cre-enhanced yellow fluorescent protein [VE-Cad-Cre-EYFP]). Treatment of tumor-bearing mice with different chemotherapeutics resulted in a three- to 10-fold increase in the influx of VE-Cad-Cre-EYFP. This enhanced influx was accompanied by a significant increase in angiogenesis. Expression profile analysis revealed a progressive change in the EYFP population with loss of endothelial markers and an increase in mononuclear markers. In the tumor, 2 specific populations of VE-Cad-Cre-EYFP BMDCs were identified: Gr1⁺/CD11b⁺ and Tie2high/platelet endothelial cell adhesion moleculelow cells, both located in perivascular areas. A common signature of the EYFP population that exits the bone marrow is an increase in Notch. Inducible inactivation of Notch in the EYFP⁺ BMDCs impaired homing of these BMDCs to the tumor. Importantly, Notch deletion reduced therapy-enhanced angiogenesis, and was associated with an increased antitumor effect of the chemotherapy. These findings revealed the functional significance of a specific population of supportive BMDCs in response to chemotherapeutics and uncovered a new potential strategy to enhance anticancer therapy.

Erythropoiesis from human embryonic stem cells through erythropoietin-independent AKT signaling.

Unlimited self renewal capacity and differentiation potential make human pluripotent stem cells (PSC) a promising source for the ex vivo manufacture of red blood cells (RBCs) for safe transfusion. Current methods to induce erythropoiesis from PSC suffer from low yields of RBCs, most of which are immature and contain embryonic and fetal rather than adult hemoglobins. We have previously shown that homodimerization of the intracellular component of MPL (ic-MPL) induces erythropoiesis from human cord blood progenitors. The goal of this study was to investigate the potential of ic-MPL dimerization to induce erythropoiesis from human embryonic stem cells (hESCs) and to identify the signaling pathways activated by this strategy. We present here the evidence that ic-MPL dimerization induces erythropoietin (EPO)-independent erythroid differentiation from hESC by inducing the generation of erythroid progenitors and by promoting more efficient erythroid maturation with increased RBC enucleation as well as increased gamma:epsilon globin ratio and production of beta-globin protein. ic-MPL dimerization is significantly more potent than EPO in inducing erythropoiesis, and its effect is additive to EPO. Signaling studies show that dimerization of ic-MPL, unlike stimulation of the wild type MPL receptor, activates AKT in the absence of JAK2/STAT5 signaling. AKT activation upregulates GATA-1 and FOXO3 transcriptional pathways with resulting inhibition of apoptosis, modulation of cell cycle, and enhanced maturation of erythroid cells. These findings open up potential new targets for the generation of therapeutically relevant RBC products from hPSC.

Evolving role of positron emission tomography (PET) in urological malignancy.

We present a review on the increasing indications for the use of positron emission tomography (PET) in uro-oncology. In this review we describe the details of the different types of PET scans, indications for requesting PET scans in specific urological malignancy and the interpretation of the results.